Hospital acquired infections are of great concern to health care providers and patients. Relatively routine surgical procedures can have disastrous health consequences when a patient acquires an infection at the surgical site, even though the underlying surgical procedure was successful. Hospitals and health care providers have instituted infection control and prevention protocols and precautions to reduce the incidence of hospital acquired infections. These include sterile fields in the operating room, instrument sterilization procedures, gowning and gloves, HEPA filtered air streams, antimicrobial wipedowns of the patient's skin surrounding the surgical site prior to initiating the procedure, cleaning protocols, etc. However, notwithstanding such procedures and protocols, whenever a medical device is used in a surgical setting, a risk of infection is created, even though the medical device itself is sterile as provided in its packaging. The risk of infection dramatically increases for invasive or implantable medical devices, such as intravenous catheters, arterial grafts, intrathecal or intracerebral shunts, meshes, sutures, sealants and prosthetic devices, which create a portal of entry for pathogens while in intimate contact with body tissues and fluids. The occurrence of surgical site infections is often associated with bacteria that colonize on a medical device and form biofilms. For example, during a surgical procedure, bacteria from the surrounding environment may enter the otherwise sterile field surrounding a surgical site and attach to a medical device that is either in contact with the patient or implanted into the patient. Bacteria can then use the implanted medical device as a pathway to surrounding tissue. Such bacterial colonization on the medical device may lead to an infection resulting in morbidity and mortality.
A number of methods for reducing the risk of infection associated with invasive or implantable medical devices have been developed that incorporate antimicrobial agents into or onto the medical devices, for example, antimicrobial coatings or compounding polymeric materials with such agents. Such devices desirably provide suffiently effective levels of antimicrobial agent to counteract any bacterial contamination that might have entered the patient for a period of time after the device is in place, including inhibiting the formation of difficult to treat biofilms. Conventional antimicrobial compositions that have been used with implantable medical devices include triclosan, silver, and chlorhexidine gluconate, and may also include antibiotics such as rifampin, minocycline, clindamycin and gentamicin. However, it can be appreciated that the use of antibiotics for this purpose raises concerns with respect to antibiotic resistance. Such resistance is typically not present with antimicrobials that are not antibiotics.
Antimicrobial compositions for use in treating medical devices are known in the art. The compositions may be applied to the devices via conventional coating processes, or may be compounded into polymer compositions used to manufacture the devices. However, a distinction is drawn between devices that are implanted into the body versus devices that may have limited contact with body tissue and bodily fluids. The toxicity of an efficacious antimicrobial composition which is useful with a device that is not designed for implantation may preclude the use of that antimicrobial in or on an implantable device. This is especially true with large implants having correspondingly large surface areas.
One particular challenge with regard to making large-sized antimicrobial implant devices, such as surgical meshes, relates to applying safe and effective amounts of antimicrobial compositions sufficient to protect the implant from bacterial colonization after implantation, while producing no harmful side effects to patients and retaining the functionality of the devices. Taurolidine is known to be a mild antibacterial agent with a history of safe internal (in vivo) use, and thus has the potential to be used safely with implantable medical devices. One challenge associated with using Taurolidine on, or in, an implantable medical device is the large quantity of the antimicrobial composition typically required in order to be efficacious. This may affect several functional aspects of the device, including the appearance (e.g., flecking) and handling (e.g., flexibility) of the device. In addition, large quantities of any antimicrobial may have some toxic effects after implantation. The degree of toxicity is often correlated with the quantity or amount of the antimicrobial present on or in the device.
The use of taurolidine is often associated with catheter or fluid locks. Protamine sulfate is also known to be used with such locks as an anticoagulant. Such uses do not contemplate long term implanted medical devices, since anticoagulants are often contraindicated for obvious reasons.
Therefore, there is a need for new and improved, safe and efficacious, antimicrobial compositions for use with implantable medical devices that have improved antimicrobial performance while utilizing decreased amounts of the compositions.